Our starting poing is the surprising observation, made in numerous mammalian species including Siamese cats and albino humans, that the visual system is abnormal in several components dealing with binocular vision when there is deficient pigmentation in the eye. Our own previous genetic studies of 15 mutations affecting pigmentation in mice have confirmed earlier suggestions that pigmentation of the pigment epithelium of the eye correlates most closely with the extent to which the midline (binocular) field of vision of each eye is represented in the epsilateral side of the brain. In hypopigmented organisms defects have been described at all levels from optic chiasm to primary visual cortex and corpus callosum. The aim of our current proposal is to take advantage of the genetic uniformity of laboratory mice and the availability of well-defined coisogenic and congenic mutant stocks to analyze what might be the primary retinal or optic axon defect from which all the other problems in visual system organization follow, according to a sort of "domino" principle. We plan to quantify the number of axons passing from retina to brain and measure, for the first time, the absolute number of contralateral and ipsilateral axons from one eye in normal and hypopigmented mice. These data will rule in or out hypotheses about axonal branching or cell death. We will also use new anatomical and embryological methods to establish when the ipsilateral axons form, which types and locations of retinal ganglion cells give rise to them, and how early the pigmentation-related abnormality is expressed, as observed directly in three-dimensionally reconstructed axons in electron micrographs of serially sectioned chiasms. We will also seek aberrations in axon trajectories in the early embryonic retina and optic stalk in serially-sectioned, reconstructed specimens. These studies require use of a computer-assisted graphics system for both quantitative and three-dimensional display functions.